Discovery of diphenyl lactam derivatives as N-type calcium channel blockers

Bioorg Med Chem Lett. 2012 Feb 15;22(4):1716-8. doi: 10.1016/j.bmcl.2011.12.100. Epub 2012 Jan 8.

Abstract

A novel series of diphenyl lactam containing calcium channel blockers is described. Extensive SAR studies resulted in compounds with low molar activity and good plasma exposure after oral dosing. Compounds 2, 6 and 7 demonstrated significant efficacy in the capsaicin model of secondary hyperalgesia following oral administration.

MeSH terms

  • Administration, Oral
  • Animals
  • Biphenyl Compounds / chemical synthesis*
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / pharmacokinetics
  • Calcium Channel Blockers / chemical synthesis*
  • Calcium Channel Blockers / chemistry
  • Calcium Channel Blockers / pharmacokinetics
  • Calcium Channels, N-Type / metabolism*
  • Drug Discovery*
  • Inhibitory Concentration 50
  • Lactams / chemical synthesis*
  • Lactams / chemistry
  • Lactams / pharmacokinetics
  • Molecular Structure
  • Piperazines / chemistry
  • Rats
  • Solubility

Substances

  • 1-(6,6-bis(4-fluorophenyl)hexyl)-4-(3,4,5-trimethoxybenzyl)piperazine
  • Biphenyl Compounds
  • Calcium Channel Blockers
  • Calcium Channels, N-Type
  • Lactams
  • Piperazines
  • biphenyl